In the era of increasing clarithromycin and metronidazole resistance, the first-line standard triple therapy (PPI-amoxicillin-clarithromycin) is currently ineffective in most settings worldwide. Vonoprazan (VPZ) is a potassium-competitive acid blocker characterized by potent and rapid acid secretion-suppressive effects and became available in Japan in 2015. In Japan, 7-days triple therapy with a PPI or VPZ, amoxicillin, and clarithromycin is used as first-line therapy. A randomized controlled trial (RCT) and systematic reviews showed superior first-line eradication success of a VPZ-based regimen over a PPI-based regimen, probably due to the increase in the potency and the rapidity of onset of VPZ. Japanese guideline now recommends replacing PPI with VPZ. Moreover, a recent network meta-analysis of published RCT of 8 first line regimens reported that VPZ triple therapy achieving cure rates of >90% is the best regimen and standard triple therapy is the least in the comparative effectiveness ranking. However, high-dose and high-frequency PPI–amoxicillin dual therapy has been reported to produce cure rates around 90% in Asian populations. Moreover, in a recent Japanese RCT, the eradication rates of the clarithromycin-resistant strain in the 7days VPZ – low dose amoxicillin dual therapy was higher than those in the VPZ -triple therapy. VPZ -dual therapy may become a potential first-line therapy in areas of high clarithromycin resistance, but optimization is still required especially for Western populations.